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Semi-Natural Rearing Conditions Alter the Trajectory of Sensorimotor Cortical Development: Functional Connectivity and Behavior

半自然饲养条件改变感觉运动皮层发育的轨迹：功能连接和行为

基本信息

批准号：
10314017
负责人：
Mackenzie Englund
金额：
$ 1.76万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-01-03 至 2022-02-28
项目状态：
已结题

项目摘要

The developing neocortex is highly malleable. Early experience tunes neural systems to match an organism’s environmental context, allowing the organism to generate adaptive behavior necessary for survival, growth, and reproduction in a changing environment. For decades, paradigms of sensory deprivation and enrichment have been used to show how early sensory input dramatically alters the connectivity and functional organization of primary sensory areas in the neocortex. How these changes in sensory input lead to changes in motor output, and how the developmental trajectory is altered to produce these changes, is unknown. Further, there are few studies that examine how differences in motor opportunities (affordances), particularly those available in large three-dimensional spaces, impact the motor system. We address this issue by rearing rats in a dynamic semi-natural environment 3000 times the size of standard laboratory cages, and quantifying changes in the connectivity and functional organization of motor cortex, and subsequent behavior, at different developmental milestones. In the current proposal, we seek to elucidate what and when specific modifications are made to motor cortex due to variations in the early postnatal environment. We will do this by comparing the emergence of sensorimotor behaviors between laboratory and semi-naturally reared rats, quantifying differences in when behavioral milestones are reached, how well animals accomplish sensorimotor tasks, and what strategies they use to do so. Following behavioral assays, we will examine differences in the intrinsic connectivity (microcircuitry) and organization of primary motor cortex (M1), assessing the distribution and density of connections between movement representations within M1. Additionally, we will examine the emergence of movement representations of different body parts within M1 at different developmental time points using intracortical microstimulation techniques. Finally, we will quantify differences in the macrocircuitry of M1, examining connectivity with other cortical fields within and across hemispheres as well as with subcortical structures. This is the first study that rears laboratory animals in a large and dynamic wild-type environment to systematically address how early experience impacts the development of motor areas of the cortex and the coordinated behaviors that the brain generates.

发育中的大脑皮层可塑性很强。早期的经验调整神经系统以匹配有机体的环境背景，允许生物体产生生存，生长，在不断变化的环境中繁殖。几十年来，感官剥夺和丰富的范例已经被用来显示早期的感觉输入是如何戏剧性地改变连接和功能的。新皮层中初级感觉区域的组织。这些感觉输入的变化是如何导致在运动输出中，以及如何改变发育轨迹以产生这些变化，都是未知的。此外，很少有研究探讨运动机会（启示）的差异，特别是那些在大的三维空间中可用的，影响运动系统。我们通过饲养来解决这个问题大鼠在一个动态的半自然环境中的3000倍大小的标准实验室笼，并量化运动皮层的连接和功能组织的变化，以及随后的行为，在不同的时间，发展里程碑在目前的提案中，我们试图阐明具体修改的内容和时间是由于出生后早期环境的变化而在运动皮层产生的。我们将通过比较实验室和半自然饲养的大鼠之间感觉运动行为的出现，在达到行为里程碑的时间，动物完成感觉运动任务的程度，以及他们使用什么策略来做到这一点。在行为分析之后，我们将研究内在的差异。连接（微电路）和初级运动皮层（M1）的组织，评估分布和 M1中运动表示之间的连接密度。此外，我们将研究不同发育时期M1内不同身体部位运动表征的出现点使用皮质内微刺激技术。最后，我们将量化宏电路的差异， M1，检查与半球内和跨半球的其他皮层区域以及与皮质下结构这是第一项在大型和动态野生型中饲养实验室动物的研究。环境，以系统地解决早期经验如何影响运动区的发展，皮层和大脑产生的协调行为。